Many of the investigations in the genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. A cohort of patients with the nevoid basal cell carcinoma syndrome and first and second degree relatives of patients with NBCC are being evaluated for the risk of cancer. Among patients with Beckwith-Wiedemann syndrome, nephromegaly conferred approximately a 50-fold increased risk of Wilm's tumor. This finding may predict a group who would benefit from more frequent screening. An investigation was conducted to determine whether the estimates of odds ratios were modified by using relatives as controls when risk factors interact with an underlying genetic factor. In the case of a common disease, the use of relatives as controls could be helpful in detecting interaction between an exposure and an underlying genetic factor when the genetic factor is common. We found that about 0.9% of Ashkenazi Jews may carry a particular germline BRCA1 mutations (named 185delAG). Risks of cancer associated with BRCA1 and BRCA2 mutations have been estimated primarily in high-risk families. A study was initiated to estimate the age-related penetrance of mutations in a broad group of individuals. Over 5,300 Ashkenazi Jews from Greater Washington volunteered for this study over a 9-week period, donating a small blood sample by finger stick and completing a questionnaire. Blood samples will be tested for the 185delAG and 5382insC mutations in BRCA1 and the 617delT mutation in BRCA2, mutations detected in Jewish breast cancer families. The family history of cancer will be compared between those who do and do not carry one of these mutations.